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5w2i

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Revision as of 10:16, 15 November 2017

Crystal structure of the core catalytic domain of human inositol phosphate multikinase soaked with C4-analogue of PtdIns(4,5)P2 and ADP

Structural highlights

5w2i is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5w2g, 5w2h
Gene:	IPMK, IMPK (HUMAN)
Activity:	Inositol-polyphosphate multikinase, with EC number 2.7.1.151
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IPMK_HUMAN] Inositol phosphate kinase with a broad substrate specificity. Has a preference for inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4).^[1] ^[2]

Publication Abstract from PubMed

Human inositol phosphate multikinase (HsIPMK) critically contributes to intracellular signaling through its inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) 3-kinase and phosphatidylinositol- 4,5-bisphosphate (PtdIns(4,5)P2) 3-kinase activities. This catalytic profile is not conserved; orthologs from Arabidopsis thaliana and Saccharomyces cerevisiae are predominantly Ins(1,4,5)P3 6-kinases, and the plant enzyme cannot phosphorylate PtdIns(4,5)P2. Therefore, crystallographic analysis of the yeast and plant enzymes, without bound inositol phosphates, do not structurally rationalize HsIPMK activities. Here, we present 1.6 A resolution crystal structures of HsIPMK in complex with either Ins(1,4,5)P3 or PtdIns(4,5)P2. The Ins(1,4,5)P3 headgroup of PtdIns(4,5)P2 binds in precisely the same orientation as free Ins(1,4,5)P3 itself, indicative of evolutionary optimization of 3- kinase activities against both substrates. We report on nucleotide binding between the separate N- and C-lobes of HsIPMK. The N-lobe exhibits a remarkable degree of conservation with protein kinase A (root mean square deviation = 1.8 A), indicating common ancestry. We also describe structural features unique to HsIPMK. First, we observed a constrained, horseshoe-shaped substrate pocket, formed from an alpha-helix, a 310 helix, and a recently evolved tri-proline loop. We further found HsIPMK activities rely on a preponderance of Gln residues, in contrast to the larger Lys and Arg residues in yeast and plant orthologs. These conclusions are supported by analyzing 14 single-site HsIPMK mutants, some of which differentially affect 3-kinase and 6- kinase activities. Overall, we structurally rationalize phosphorylation of Ins(1,4,5)P3 and PtdIns(4,5)P2 by HsIPMK.

Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities.,Wang H, Shears SB J Biol Chem. 2017 Sep 7. pii: jbc.M117.801845. doi: 10.1074/jbc.M117.801845. PMID:28882892^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nalaskowski MM, Deschermeier C, Fanick W, Mayr GW. The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization. Biochem J. 2002 Sep 1;366(Pt 2):549-56. PMID:12027805 doi:http://dx.doi.org/10.1042/BJ20020327
↑ Chang SC, Miller AL, Feng Y, Wente SR, Majerus PW. The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase. J Biol Chem. 2002 Nov 15;277(46):43836-43. Epub 2002 Sep 9. PMID:12223481 doi:http://dx.doi.org/10.1074/jbc.M206134200
↑ Wang H, Shears SB. Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities. J Biol Chem. 2017 Sep 7. pii: jbc.M117.801845. doi: 10.1074/jbc.M117.801845. PMID:28882892 doi:http://dx.doi.org/10.1074/jbc.M117.801845

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5w2i"

@@ Line 3: / Line 3: @@
 <StructureSection load='5w2i' size='340' side='right' caption='[[5w2i]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w2i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w2i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2I FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w2g|5w2g]], [[5w2h|5w2h]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IPMK, IMPK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Inositol-polyphosphate_multikinase Inositol-polyphosphate multikinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.151 2.7.1.151] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5w2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w2i OCA], [http://pdbe.org/5w2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w2i RCSB], [http://www.ebi.ac.uk/pdbsum/5w2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w2i ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Inositol-polyphosphate multikinase]]
 [[Category: Shears, S B]]

5w2i

From Proteopedia

Revision as of 10:16, 15 November 2017

Crystal structure of the core catalytic domain of human inositol phosphate multikinase soaked with C4-analogue of PtdIns(4,5)P2 and ADP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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